This protocol evaluated the safety, tolerance, cell kinetics, and anti-HIV activity of autologous red blood cells (RBC's) which were modified ex vivo by electroinsertion of full-length recombinant CD4 expressed by a bacullovirus expression vector system. This protocol enrolled 19 HIV- infected subjects, who donated from 100 to 400 cc of blood for electroinsertion. Three subjects had an aliquot of modified RBC's labeled with 51-chromium for measurement of RBC survival. We found that electroinsertion of full-length CD4 did not significantly alter RBC survival in treated subjects. Treatment was well-tolerated and produced no significant adverse events. Plasma HIV RNA did not change significantly in these subjects, although there was a transient fall in HIV recovery from whole blood in some subjects. This study has demonstrated the feasibility of using autologous RBC's as a carrier for biologically active surface proteins with therapeutic potential. This protocol is now completed.